Certain embodiments are directed to the fields of chemistry and oncology. Certain aspects are directed to anti-cancer and anti-inflammatory compounds.
Natural products have a profound impact upon both chemical biology and drug discovery, and the great structural diversity of natural products at various levels has always served medicinal chemists as a source of inspiration in their search for new molecular entities with pharmacological activity (Newman, J. Med. Chem. 2008, 51:2589-99). Natural tetracyclic diterpenoids, especially ent-kaurane diterpenoids with an enone system in ring D such as oridonin (1) and eriocalyxin B, constitute an important class of natural products which exhibit considerable pharmacological activities including anti-tumor and anti-inflammatory effects (Nagashima et al., Tetrahedron 2005, 61:4531-44; Huang et al., J. Nat. Prod. 2005, 12:1758-62; Li et al., Phytochemistry 2006, 13:1336-40).
Structurally, the highly oxygenated oridonin, belonging to 7, 20-epoxy-ent-kaurane-type diterpenoid, is primarily characterized with an α,β-unsaturated ketone moiety in ring D and a 6-hydroxyl-7-hemiacetal group, which is stereochemically rich and densely functionalized. To date, reported structure modifications are primarily focused on the 1-O and 14-O positions, likely due to synthetic ease (Xu et al., Bioorg. Med. Chem. Lett. 2008, 18:4741-44). There remains a need for development of additional oridonin analogs.